Cam M C, Brownsey R W, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia,Vancouver, Canada.
Can J Physiol Pharmacol. 2000 Oct;78(10):829-47.
The demonstration that the trace element vanadium has insulin-like properties in isolated cells and tissues and in vivo has generated considerable enthusiasm for its potential therapeutic value in human diabetes. However, the mechanisms by which vanadium induces its metabolic effects in vivo remain poorly understood, and whether vanadium directly mimics or rather enhances insulin effects is considered in this review. It is clear that vanadium treatment results in the correction of several diabetes-related abnormalities in carbohydrate and lipid metabolism, and in gene expression. However, many of these in vivo insulin-like effects can be ascribed to the reversal of defects that are secondary to hyperglycemia. The observations that the glucose-lowering effect of vanadium depends on the presence of endogenous insulin whereas metabolic homeostasis in control animals appears not to be affected, suggest that vanadium does not act completely independently in vivo, but augments tissue sensitivity to low levels of plasma insulin. Another crucial consideration is one of dose-dependency in that insulin-like effects of vanadium in isolated cells are often demonstrated at high concentrations that are not normally achieved by chronic treatment in vivo and may induce toxic side effects. In addition, vanadium appears to be selective for specific actions of insulin in some tissues while failing to influence others. As the intracellular active forms of vanadium are not precisely defined, the site(s) of action of vanadium in metabolic and signal transduction pathways is still unknown. In this review, we therefore examine the evidence for and against the concept that vanadium is truly an insulin-mimetic agent at low concentrations in vivo. In considering the effects of vanadium on carbohydrate and lipid metabolism, we conclude that vanadium acts not globally, but selectively and by enhancing, rather than by mimicking the effects of insulin in vivo.
微量元素钒在离体细胞、组织及体内具有胰岛素样特性，这一发现引发了人们对其在人类糖尿病治疗中潜在价值的极大热情。然而，钒在体内诱导代谢效应的机制仍知之甚少，本文将探讨钒是直接模拟胰岛素作用还是增强胰岛素效应。显然，钒治疗可纠正碳水化合物和脂质代谢以及基因表达中与糖尿病相关的多种异常。然而，这些体内胰岛素样效应中的许多可归因于高血糖继发缺陷的逆转。钒的降糖作用依赖内源性胰岛素的存在，而对照动物的代谢稳态似乎未受影响，这表明钒在体内并非完全独立发挥作用，而是增强了组织对低水平血浆胰岛素的敏感性。另一个关键因素是剂量依赖性，因为在离体细胞中，钒的胰岛素样效应通常在高浓度下才能显现，而这种浓度在体内长期治疗中通常无法达到，且可能会引发毒副作用。此外，钒似乎对某些组织中胰岛素的特定作用具有选择性，而对其他组织则无影响。由于钒的细胞内活性形式尚未明确界定，钒在代谢和信号转导途径中的作用位点仍然未知。因此，在本文中，我们将审视支持和反对钒在体内低浓度时是真正胰岛素模拟剂这一概念的证据。在考虑钒对碳水化合物和脂质代谢的影响时，我们得出结论：钒并非全局性地发挥作用，而是具有选择性，且在体内是通过增强而非模拟胰岛素的作用来发挥效应。
